The proposed studies will characterize prostatic nitric oxide an explore its potential role in prostatic function. Because of its properties as a neurotransmitter, messenger molecule, vasodilator and cytotoxic agent, nitric oxide and its synthetic enzyme nitric oxide synthase may plan a significant yet diverse role in modulating prostatic function and development. Similar to its actions as a neurotransmitter in the central nervous system, nitric oxide may influence prostatic function through mechanisms attributed earlier to adrenergic, cholinergic and non-adrenergic non-cholinergic neuronal systems. Alternatively, nitric oxide may relax prostatic smooth muscle in a manner similar to alpha-adrenergic blockers used in the treatment of BPH. Finally, because it can induce cell death in a variety of tissues, nitric oxide may play a role in the control of prostate development, in the involution of the gland following androgen ablation, or in the development of BPH. To better understand the role of nitric oxide and nitric oxide synthase in the prostate we propose: 1) to characterize prostatic NOS in the rat and in a canine model for benign prostatic hyperplasia (BPH); 2) to examine the androgen regulation of NOS within the rat prostate; 3) to determine whether NOS co-localizes with neuroendocrine cells within the prostate; 4) to test the hypothesis that NO may be involved in castration-induced prostatic involution; and 5) to examine the role of NO in prostatic secretory function and in prostatic smooth muscle relaxation. The information acquired in these studies will provide new insight into the physiology of the prostate and may have profound implications regarding athe development of new approaches to the treatment of BPH.